Organ-specific features of natural killer cells.
Organ-specific features of natural killer cells.
复制标题
DOI：
10.1038/nri3065
复制
发表时间：
2011-09-23
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
自然杀伤（NK）细胞可以被危险信号迅速动员，是最早到达疾病靶器官的细胞之一。然而，NK细胞在调节炎症反应中的作用在不同器官中还远未完全了解。它往往是复杂的，有时是矛盾的。NK细胞在肝脏、粘膜组织、子宫、胰腺、关节和大脑中的表型和功能受到每个器官内独特的细胞相互作用和局部微环境的影响。肝NK细胞表现出具有高水平细胞毒性效应分子的活化表型。这些细胞与促进肝损伤和抑制肝纤维化和再生有关。肝脏也富含具有记忆样适应性免疫特征的NK细胞。NK细胞在肺、皮肤和肠道的健康淋巴组织中被检测到，并在感染或炎症期间被招募到这些组织中。在胃肠道中，经典的NK细胞和各种先天性淋巴细胞，如淋巴组织诱导（LTi）细胞家族，可能在控制炎症反应中发挥关键作用。NK细胞代表妊娠子宫中的主要淋巴细胞亚群，具有类似于早期发育状态的独特表型。新的证据表明，这些细胞在介导子宫血管适应妊娠和促进维持健康妊娠方面起着至关重要的作用。在非肥胖糖尿病（NOD）小鼠中，NK细胞早期被募集到胰腺，局部活化，然后采用低反应表型。虽然NK细胞在NOD小鼠糖尿病的自然进展中具有致病作用，但它们有助于完全弗氏佐剂诱导的糖尿病保护和共刺激阻断诱导的胰岛同种异体移植耐受。炎症关节中的NK细胞独特地表达NF-κB配体受体激活因子（RANKL）和巨噬细胞集落刺激因子（M-CSF），其促进破骨细胞分化。尽管NK细胞在小鼠胶原诱导的关节炎中具有致病作用，但它们对于保护免受CpG寡核苷酸介导的抗体诱导的关节炎也至关重要。在多发性硬化症小鼠模型中的研究表明，NK细胞在致病性T细胞之前到达中枢神经系统（CNS），并在CNS炎症的发展中具有保护作用，可能是通过杀死引发效应T细胞的CNS驻留小胶质细胞。在进化过程中，不同的器官可能进化出不同的方式来招募和影响NK细胞的效应功能。一旦我们了解了这些机制，下一个挑战将是利用这些信息来利用NK细胞来开发针对感染因子，肿瘤和炎症性疾病的预防和治疗措施。我们身体中的每个组织都包含一个独特的微环境，可以不同地塑造免疫反应性。在这篇综述文章中，Shiet al.描述了器官特异性因素如何影响自然杀伤细胞归巢和表型，并讨论了决定不同组织中自然杀伤细胞保护或致病功能的局部分子和细胞相互作用。自然杀伤（NK）细胞可以被危险信号迅速动员，是最早到达疾病靶器官的细胞之一。然而，NK细胞在炎症反应中的作用往往是复杂的，有时是矛盾的。在这里，我们研究了不同的表型和NK细胞的功能特征，主要是从实验小鼠模型的病理生理反应，在肝脏，粘膜组织，子宫，胰腺，关节和大脑推导。此外，我们还讨论了器官特异性因素、局部微环境和独特的细胞相互作用如何影响NK细胞的器官特异性特性。
Natural killer (NK) cells can be swiftly mobilized by danger signals and are among the earliest arrivals in target organs of disease. However, the role of NK cells in regulating inflammatory responses is far from completely understood in different organs. It is often complex and sometimes paradoxical. The phenotypes and functions of NK cells in the liver, mucosal tissues, uterus, pancreas, joints and brain are influenced by the unique cellular interactions and the local microenvironment within each organ. Hepatic NK cells exhibit an activated phenotype with high levels of cytotoxic effector molecules. These cells have been implicated in promoting liver injury and inhibiting liver fibrosis and regeneration. The liver is also enriched in NK cells with memory-like adaptive immune features. NK cells are detected in healthy lymphoid tissues of the lung, skin and gut, and are recruited to these tissues during infection or inflammation. In the gastrointestinal tract, classical NK cells and a variety of innate lymphoid cells, such as the family of lymphoid tissue-inducer (LTi) cells, are likely to have crucial roles in controlling inflammatory responses. NK cells represent the major lymphocyte subset in the pregnant uterus, with a unique phenotype resembling an early developmental state. Emerging evidence indicates that these cells play a crucial part in mediating the uterine vascular adaptations to pregnancy and promoting the maintenance of healthy pregnancy. In non-obese diabetic (NOD) mice, NK cells are recruited early to the pancreas, become locally activated and then adopt a hyporesponsive phenotype. Although NK cells have a pathogenic role in the natural progression of diabetes in NOD mice, they contribute to diabetes protection induced by complete Freund's adjuvant and to islet allograft tolerance induced by co-stimulatory blockade. NK cells in the inflamed joint uniquely express receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), which promote osteoclast differentiation. Although NK cells have a pathogenic role in collagen-induced arthritis in mice, they are also crucial for protection against antibody-induced arthritis mediated by CpG oligonucleotides. Studies in a mouse model of multiple sclerosis have shown that NK cells arrive in the central nervous system (CNS) before pathogenic T cells and have a protective role in the development of CNS inflammation, probably by killing CNS-resident microglia that prime effector T cells. During evolution, different organs might have evolved distinct ways to recruit and influence the effector functions of NK cells. Once we understand these mechanisms, the next challenge will be to exploit this information for harnessing NK cells to develop prophylactic and therapeutic measures against infectious agents, tumours and inflammatory diseases. Each tissue in our body contains a unique microenvironment that can differentially shape immune reactivity. In this Review article, Shiet al. describe how organ-specific factors influence natural killer cell homing and phenotype, and discuss the local molecular and cellular interactions that determine the protective or pathogenic functions of natural killer cells in the different tissues. Natural killer (NK) cells can be swiftly mobilized by danger signals and are among the earliest arrivals at target organs of disease. However, the role of NK cells in mounting inflammatory responses is often complex and sometimes paradoxical. Here, we examine the divergent phenotypic and functional features of NK cells, as deduced largely from experimental mouse models of pathophysiological responses in the liver, mucosal tissues, uterus, pancreas, joints and brain. Moreover, we discuss how organ-specific factors, the local microenvironment and unique cellular interactions may influence the organ-specific properties of NK cells.
登录
查看更多内容
影响因子：
8.7
作者：
Cooper MA;Yokoyama WM
通讯作者：
Yokoyama WM
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
15.3
作者：
Ashkar, A A;Di Santo, J P;Croy, B A
通讯作者：
Croy, B A
影响因子：
--
作者：
Bielekova, Bibiana;Howard, Thomas;Packer, Amy N.;Richert, Nancy;Blevins, Gregg;Ohayon, Joan;Waldmann, Thomas A.;McFarland, Henry F.;Martin, Roland
通讯作者：
Martin, Roland
影响因子：
20.3
作者：
Fauriat, Cyril;Long, Eric O.;Bryceson, Yenan T.
通讯作者：
Bryceson, Yenan T.